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11820en-us2014-05-06T11:35:11ZTue, 06 May 2014 11:35:11 +0000hourly12000-01-01T12:00+00:00A Plea for Researchhttp://neurology.about.com/b/2014/05/06/a-plea-for-research.htm
<p>The About.com Neurology website is changing. As part of that change, blog entries are going away to allow more emphasis on long-form content. I will use one last blog entry to make an entreaty that would not fit well in another form.
<p>If you are visiting this website, the chances are very high that you or someone you know has been impacted by at least one of the many neurological illnesses for which there is still no cure. While we have made incredible strides forward, there is much to be learned. We cannot do this without the support of our community, who should, in my opinion, include anyone with a brain and an interest in keeping it healthy.
<p>I confess that there is something of a conflict of interest in what I ask. I am primarily a researcher. I do this because I believe that diseases of the brain and nervous system are uniquely important even among all other medical problems. I believe that a life dedicated to better understanding how our minds work is a life well spent, and that finding cures to diseases of the brain are all the more noble. To paraphrase, "what does it profit a person to save the rest of their body and lose their mind?"
<p>There are dozens of organizations committed to improving the lives of those with neurological illnesses. I will not play favorites here--each organization offers unique opportunities to benefit both people now in need as well as the future of humanity as a whole. There are too many worthy organizations for me to list, and if you as a reader would like something included not listed below, don't hesitate to include it in the comments section.
<ul>
<p><li><a href="http://clk.about.com/?zi=1/1hc&#038;zu=http://www.ninds.nih.gov/about_ninds/gift_fund.htm ">The National Institute for Neurological Disorders and Stroke</a>
<li><a href="http://clk.about.com/?zi=1/1hc&#038;zu=http://americanbrainfoundation.org/">The American Brain Foundation</a>
<li><a href="http://clk.about.com/?zi=1/1hc&#038;zu=http://www.alz.org/join_the_cause_donate.asp">The Alzheimer's Association</a>
<li><a href="http://clk.about.com/?zi=1/1hc&#038;zu=https://www.aesnet.org/about_aes/contribute">The American Epilepsy Society</a>
<li><a href="http://clk.about.com/?zi=1/1hc&#038;zu=http://www.pdf.org/fund_memdon">The Parkinson's Disease Foundation </a>
<li><a href="http://clk.about.com/?zi=1/1hc&#038;zu=http://mda.org/ways-to-help">Muscular Dystrophy Association</a>
<li><a href="http://clk.about.com/?zi=1/1hc&#038;zu=https://secure2.convio.net/bts/site/Donation2?df_id=4300&#038;4300.donation=form1">The National Brain Tumor Society </a>
<li><a href="http://clk.about.com/?zi=1/1hc&#038;zu=http://www.alsa.org/donate/">The ALS Association</a>
</ul>
<p>Together we can find treatments and maybe even cures for these terrible disorders, improving both the quantity and quality of millions of lives. http://neurology.about.com/b/2014/05/06/a-plea-for-research.htmTue, 06 May 2014 11:46:13 +00002014-05-06T11:46:13ZUpdates on Duchenne Muscular Dystrophy Drugs in Developmenthttp://neurology.about.com/b/2014/05/06/updates-on-duchenne-muscular-dystrophy-drugs-in-development.htm
<p>The FDA's decision to not approve medications intended to treat Duchenne muscular dystrophy (DMD) sparked outrage earlier this year from many familiar with the disorder. While medications area an urgent need, the FDA did not believe the level of evidence was sufficient for approval at that time. Further evidence, however, may lead to a re-consideration of that decision.
<p>Two drugs were being intensively studied: drisapersen and eteplirsen. Results for drisapersen were more problematic earlier this year. Prolonged trials suggest a benefit only in one group of patients. In boys aged 5 to 6 years old, the mean 6-minute walking distance continued to decline, though seemingly at a slower rate than those who took placebo for half that time. I have to say seemingly because the difference was not found to be statistically significant, meaning that it could have been due to chance. That said, the trend was suggestive, and one group in western Europe who stayed on the drug for 96 weeks showed no decline.
<p>In addition to geographic location, this more successfully treated group was aged 5 to 11, as opposed to 5 to 16 in the group that showed no difference. This suggests that there may be genetic factors that contribute to the successful use of drisapersen, and that the drug may be more efficacious if given at a young age. Children younger than 7 showed no decline in the walking test when on the drug. That said, the study was not designed to clearly demonstrate these effects, and so definitive answers remain frustratingly elusive. However, the developers of the drug do believe that they can persevere and eventually win approval.
<p>Results for eteplirsen are more immediately promising. The mean 6 minute walk distance has been preserved for 120 weeks in six boys who took the drug over tha t period of time. Four boys who initially took placebo and then switched showed a strong change initially, but then stabilized, again suggesting that this approach may best be started early. Pulmonary function was preserved over 120 weeks in both groups, compared to weakness leading to decreases of 4% annually in historical controls.
<p>Sarepta, the company developing the drug, recently reached an agreement with the FDA. The FDA remains open to an accelerated approval, and might allow a New Drug Application to be filed later this year, provided that new trials be done in patients under the age of 7, confirmatory trials in those 7-16 with clinical efficacy endpoints, and in those who cannot complete a 6MWD evaluation. This is a softening from the previous position that it could not consider approving the drug based on the nonclinical primary endpoint of the previous trial. Perhaps the FDA is beginning to recognize the need to make exceptions for rare diseases in which numbers may be too small for more traditional methods.
<p>Source:
<p>Kaye E, et al "Results at 96 weeks of a phase iib extension study of the exon-skipping drug eteplirsen in patients with Duchenne Muscular Dystrophy (DMD)" AAN 2014; Abstract S6.002.
http://neurology.about.com/b/2014/05/06/updates-on-duchenne-muscular-dystrophy-drugs-in-development.htmTue, 06 May 2014 11:35:11 +00002014-05-06T11:35:11ZExploring Dystonia's Geste Antagonistehttp://neurology.about.com/b/2014/05/06/exploring-dystonias-geste-antagoniste.htm
<p><a href="http://clk.about.com/?zi=1/1hc&#038;zu=http://neurology.about.com/od/Movement/a/Introduction-To-Dystonia.htm">Dystonia</a> is an uncomfortable fixed posturing of part of the body. Examples include writer's cramp or cervical torticollis.
<p>Many people with dystonia find relief in a sensory trick called the <i>geste antagoniste</i>. Touching part of the body, usually the one that is dystonic, can partially relax the muscular tension in 43% of patients, and completely relieve the dystonia in 40% according to research done by Neepa Patel, MD.
<p>Most of the sensory tricks were on the face, chin or neck on the same side as the tension. Others, however, find relief by touching areas further from the dystonic region.
<p>A separate group, led by Ubaldo Del Carro of Ospedale San Raffaele Scientific Institute in Milan, used transcranial magnetic stimulation (TMS) to further investigate the neural underpinnings of the geste antagoniste. TMS of the motor cortex of patients with cervical dystonia was used in conjunction with electrophysiological measurements of the other hand. When the patients used a <i>geste antagoniste</i>, facilitation was reduced, suggesting that overactivity of the motor cortex had been reduced.
<p>I've suspected for years that many of what are traditionally called "movement disorders" actually involve much more than the parts of the brain responsible for movement. Some may in fact be disorders of sensorimotor integration, meaning how our sensation informs and guides our movements. For example, in Parkinson's disease, someone may be unable to start walking until they look down and step over something. All that was needed was another route of sensory input to trigger the movement. This is an underappreciated area of research, and one that could have large implications to patients as well as our knowledge of these diseases and the brain itself.
<p>Sources:
<p>Amadio S, et al "Sensory tricks reverse intracortical facilitation changes in cervical dystonia. A transcranial magnetic stimulation study" AAN 2014; Abstract P2.047.
<p>Patel N, et al "Alleviating maneuvers (sensory tricks) in cervical dystonia" AAN 2014; Abstract P2.046.
<p>Ramos V, et al "Tricks to treatments: Sensory tricks in dystonia" AAN 2014; Abstract P2.042.
http://neurology.about.com/b/2014/05/06/exploring-dystonias-geste-antagoniste.htmTue, 06 May 2014 11:27:35 +00002014-05-06T11:27:35ZOfatumumab Found to Reduce MS Lesionshttp://neurology.about.com/b/2014/05/06/ofatumumab-found-to-reduce-ms-lesions.htm
<p>Multiple sclerosis used to be thought to be predominantly driven by T-cells, <a href="http://clk.about.com/?zi=1/1hc&#038;zu=http://biology.about.com/od/cellbiology/ss/lymphocytes.htm">lymphocytes</a> that are meant to recognize, bind to and sometimes terminate cells containing harmful substances (antigens). Sometimes, T-cells mistake a naturally occurring part of the body for a foreign invader, leading to an autoimmune response. This is a large part of the theory behind <a href="http://clk.about.com/?zi=1/1hc&#038;zu=http://ms.about.com/od/multiplesclerosis101/a/ms_intro.htm">multiple sclerosis</a>.
<p>Within the last decade or so, multiple sclerosis researchers have also begun to recognize the significance of B-cells, another component of the immune system. Unlike T-cells, B-cells do not directly attack antigens, but create antibodies to label those antigens.
<p><a href="http://clk.about.com/?zi=1/1hc&#038;zu=http://arthritis.about.com/od/mabtherarituxan/">Rituximab</a> is a drug sometimes used in MS that works by changing B-cells. Ofatumumab is another B-cell targeting agent, which was recently demonstrated to significantly reduce new brain lesions. Clinical endpoints remain to be reported. At 24 weeks, 6% of research participants had severe adverse effects when they took the medication at a high dose, compared to no more than 3% in a lower dose. Those side effects included infections and dizziness.
<p>Source:
<p>Bar-Or A, et al "The MIRROR Study: A randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study to investigate the safety and MRI efficacy of subcutaneous ofatumumab in subjects with relapsing-remitting multiple sclerosis (RRMS)" AAN 2014; Abstract S23.006.
http://neurology.about.com/b/2014/05/06/ofatumumab-found-to-reduce-ms-lesions.htmTue, 06 May 2014 11:20:41 +00002014-05-06T11:20:41ZNew Technique in Diagnosing Meningoencephalitishttp://neurology.about.com/b/2014/05/02/new-technique-in-diagnosing-meningoencephalitis.htm
<p><a href="http://clk.about.com/?zi=1/1hc&#038;zu=http://neurology.about.com/od/Meningitis/a/Aseptic-Meningitis.htm">Meningoencephalitis</a>, meaning inflammation of the brain and its surrounding tissues, causes 20,000 hospitalizations annually, with a cost of about 2 billion dollars for care in the hospital. Overall mortality is 6%, which goes up to 10% mortality with <a href="http://clk.about.com/?zi=1/1hc&#038;zu=http://neurology.about.com/od/ID/a/Neurological-Complications-Of-Hiv.htm">HIV coinfection</a>, and 17% with organ transplants. Over half of these cases are never explained by diagnostic tests.
<p>Meningoencephalitis is caused by over 100 pathogens which vary by geography, season, and individual demographics. Viruses are the largest cause. 50% of emerging viruses, meaning those that are either entirely unknown or are appearing in a new location or population, can produce severe neurological symptoms such as paralysis or seizures. Examples include West Nile Virus, JC virus, arena viruses, dengue and HHV6.
<p>Viruses and other causes of meningoencephalitis can be very hard to diagnose. Polymerase chain reaction (PCR) looks for particular strands of viral DNA within the patient, and is often useful. Viral culture and tissue biopsy may be attempted if this fails, but these tend to be less productive.
<p>Next Generation Sequencing (NGS) is an emerging technique used in the diagnosis of meningoencephalitis among other disorders. This sequences all nucleic acids within a sample. If given a bit of cerebrospinal fluid, for example, NGS looks at all the genetic information available. Complex bioinformatics computing then filters out human DNA from foreign genetic material, including viruses.
<p>Unlike PCR, NGS looks at all genes rather than aiming for specific viruses. This allows NGS to identify rare and even new viruses that could be causing someone's illness.
<p>There are some concerns about this new technology, however. The technique is by nature overly sensitive--it frequently finds too much information. For example, it may find several viruses that do not cause problems in humans, but only plants--the patient may have been exposed, but there's no danger.
<p>At this time, such testing is usually reserved for research, which raises some ethical and regulatory issues. How, if ever, should these techniques be used in clinical care? At this time, people who want this testing may enroll in research. This should especially be considered in cases of meningoencephalitis of unknown cause despite thorough clinical testing.
<p>Source:
<p>Michael Wilson, MD. UCSF Memory and Aging Center Grand Rounds, Rock Hall Auditorium, San Francisco, February 28, 2014
http://neurology.about.com/b/2014/05/02/new-technique-in-diagnosing-meningoencephalitis.htmFri, 02 May 2014 13:29:59 +00002014-05-02T13:29:59ZNews from the AAN Annual Conferencehttp://neurology.about.com/b/2014/04/30/news-from-the-aan-annual-conference.htm
I'm currently in Philadelphia for the American Academy of Neurology annual conference. You can expect to hear more from me in coming days about some of the science that's ...<p><a href="http://clk.about.com/?zi=1/1hc&#038;zu=http://neurology.about.com/b/2014/04/30/news-from-the-aan-annual-conference.htm">Read Full Post</a></p>http://neurology.about.com/b/2014/04/30/news-from-the-aan-annual-conference.htmWed, 30 Apr 2014 23:31:34 +00002014-04-30T23:31:34ZNotes from the Society for Affective Sciencehttp://neurology.about.com/b/2014/04/30/notes-from-the-society-for-affective-science.htm
Last week I attended the the inaugural meeting of the Society for Affective Science. Years ago, cognitive science was born to explain the various aspects of cognition. A ...<p><a href="http://clk.about.com/?zi=1/1hc&#038;zu=http://neurology.about.com/b/2014/04/30/notes-from-the-society-for-affective-science.htm">Read Full Post</a></p>http://neurology.about.com/b/2014/04/30/notes-from-the-society-for-affective-science.htmWed, 30 Apr 2014 17:44:28 +00002014-04-30T17:44:28ZIndications for Warfarin after Stroke are Dwindlinghttp://neurology.about.com/b/2014/04/30/indications-for-warfarin-after-stroke-are-dwindling.htm
<p>For many, warfarin can be a lifesaving drug. The blood thinner can be very effective at reducing the chance of <a href="http://clk.about.com/?zi=1/1hc&#038;zu=http://neurology.about.com/od/Symptoms/a/Symptoms-Of-A-Stroke.htm">stroke</a> in people with atrial fibrillation or atrial flutter.
<p>That said, I confess that I dislike this medication. Simply put, it is a pain to manage. A blood value, the international ratio (INR) reflects the drug's efficacy, and must be kept within a fairly tight range of values. Too little and the drug doesn't work, too much and the patient's blood won't clot in the face of even minor injury, inviting disaster. An otherwise slight cut or a bump on the head can turn into a major bleed.
<p>A narrow dose level wouldn't be such a problem except that the drug has many potentials for interactions. Leafy green vegetables, for example, can drop warfarin's efficacy. Many other medications can interact with warfarin, changing how both drugs work. As a result, frequent lab checks are needed with those who are on this medication just to ensure that the level is kept constant.
<p>That said, in some situations, the medication is critical. In many others, though, it is probably over-used. For example, warfarin is often used in patients with heart failure with an ejection fraction under 35, despite a trial (WARCEF 2012) showing it does no good in preventing strokes in such patients. In a patent foramen ovale (PFO) with associated aneurysm, there are three trials that show closing have no benefit over anticoagulants like warfarin, and these anticoagulants have no benefit over anti-platelet agents such as aspirin.
<p>In arterial dissection, there is no real evidence of warfarin's benefit over anti-platelet agents, though many will still do a period such as 3 months on anticoagulation based off clinical instinct, then switch. Another situation in which warfarin is commonly prescribed is when large loose fatty plaques called atheromas sit in the aortic arch, ready to break off and float into the brain. Even in this case, a clinical trial (ARCH 2013) showed that warfarin perhaps did slightly worse than anti-platelet therapy.
<p>There's a host of new medications now being used in place of warfarin even for atrial fibrillation. For those who are stable on warfarin, there may be no reason to switch. For everyone else, though, the rationale for warfarin after stroke is slowly disappearing.
http://neurology.about.com/b/2014/04/30/indications-for-warfarin-after-stroke-are-dwindling.htmWed, 30 Apr 2014 14:07:42 +00002014-04-30T14:07:42ZProlonged Cardiac Monitoring After Stroke Detects More Arrhythmiahttp://neurology.about.com/b/2014/04/24/1124.htm
<p>When someone has a stroke, a medical exploration is done to uncover the reason for that stroke. For example, sometimes a stroke is simply due to a fatty plaque building up in an artery until the blood flow stops, resulting in tissues beyond the blockage dying due to lack of oxygen.
<p>Sometimes the blockage results from a clot that travels from somewhere else in the body, such as the heart. For example, a clot may form due to <a href="http://clk.about.com/?zi=1/1hc&#038;zu= http://stroke.about.com/od/causesofstroke/a/AFIB.htm">atrial fibrillation</a>, which is an arrhythmia that results in decreased efficiency of blood flow from the heart. Stationary blood is more likely to spontaneously clot, forming a thrombus that can then move from the heart into the brain.
<p>About 30 percent of the time, no cause of the stroke is found. In such a case, the term "cryptogenic" is used to signify our lack of knowledge about the stroke's source. It is more difficult to appropriately treat such strokes, since we do not know where to target the therapy.
<p>A recent trial, CRYSTAL-AF, investigated over 440 patients with cryptogenic stroke. All of these patients received that standard 24 hours of cardiac monitoring after the stroke to look for arrhythmia such as atrial fibrillation.
<p>Half of the patients were then tracked with an implantable heart monitor called Reveal XT, which was placed just under the skin during a minimally invasive procedure. The device is capable of continuous monitoring for up to 3 years.
<p>After 6 months, almost 9% of those with the device were found to have atrial fibrillation compared to 1.4% of those without the device. After 3 years, atrial fibrillation was found in 30% of those with the implanted monitor--ten times more than were detected in the control group. The median time to detecting arrhythmia was 84 days.
<p>Those who were found to have atrial fibrillation were placed on a <a href="http://clk.about.com/?zi=1/1hc&#038;zu= http://heartdisease.about.com/library/weekly/aa080601a.htm">stronger stroke preventative</a> than they would otherwise have received, thereby reducing their risk of another stroke in the future. Statistically, such medication reduces the risk by 70% compared to standard care for cryptogenic stroke.
<p>Only 2.4% of the devices had to be removed due to complications and there were no long-term problems. There are other concerns, though. At about $4000 per unit, the devices may be prohibitively expensive. Whether atrial fibrillation that is so infrequent as to require such monitoring poses the same kind of risks as more frequent atrial fibrillation is also unclear. While the device is minimally invasive, it is invasive. That said, a smaller version that is easier to implant is currently under review.
<p>This could be the future of cardiac monitoring after stroke, and could be a boon to reducing repeat strokes. I look forward to seeing what the future will hold for this technology.
http://neurology.about.com/b/2014/04/24/1124.htmThu, 24 Apr 2014 08:56:31 +00002014-04-24T08:56:31ZShould Aspirin and Clopidogrel be Used Together After Stroke?http://neurology.about.com/b/2014/04/18/should-aspirin-and-clopidogrel-be-used-together-after-stroke.htm
<p>When I was a resident, we normally started someone on aspirin if they weren't on it when they had a stroke. If they were, we might consider switching to a different drug, such as clopidogrel. We almost never used the two together, as the thought was that this would increase the risk of bleeding without reducing the chance of someone getting stroke in the future.
<p>Then came the recent CHANCE Trial. This large trial involved 5170 people with transient ischemic attacks (TIA) or small strokes, who were given either aspirin or both aspirin and clopidogrel. The outcome was better in the group treated with both drugs together.
<p>Interestingly, despite being a well-designed trial, results have not been replicated outside of China. For example, a recently published trial in Neurology found no such benefit to combined therapy with aspirin and clopidogrel after small strokes.
<p>Perhaps there is something unique about the population that was studied--can the results be generalized to people elsewhere? A subsequent trial, the POINT trial, is currently underway to clarify that question.
<p>Wang Y, Johnston SC, Wang Y. Clopidogrel with aspirin in minor stroke or transient ischemic attack. N Engl J Med. 2013 Oct 3;369(14):1376-7. doi: 10.1056/NEJMc1309713.
http://neurology.about.com/b/2014/04/18/should-aspirin-and-clopidogrel-be-used-together-after-stroke.htmFri, 18 Apr 2014 08:54:58 +00002014-04-18T08:54:58Z